Genetic Variant MRM2:p.Ser11Cys (chr7-2239684-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013393.3(MRM2):c.32C>G(p.Ser11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S11F) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRM2
NM_013393.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.163

Publications

0 publications found

Variant links:

Genes affected

MRM2 (HGNC:16352): (mitochondrial rRNA methyltransferase 2) The protein encoded by this gene is a member of the S-adenosylmethionine-binding protein family. It is a nucleolar protein and it may be involved in the processing and modification of rRNA. This gene has been suggested to be involved in cell cycle control and DNA repair. [provided by RefSeq, Jul 2008]

MRM2 Gene-Disease associations (from GenCC):

mitochondrial DNA depletion syndrome 17
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MRM2 links:

ENSG00000286192 (HGNC:):

ENSG00000286192 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14554694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRM2	NM_013393.3	MANE Select	c.32C>G	p.Ser11Cys	missense	Exon 2 of 3	NP_037525.1	Q9UI43

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRM2	ENST00000242257.14	TSL:1 MANE Select	c.32C>G	p.Ser11Cys	missense	Exon 2 of 3	ENSP00000242257.8	Q9UI43
MRM2	ENST00000486040.1	TSL:1	n.32C>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000498090.1	A0A3B3ITW8
ENSG00000286192	ENST00000651235.1		n.32C>G		non_coding_transcript_exon	Exon 2 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111092

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.098

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.63

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

PhyloP100

0.16

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.24

REVEL

Benign

0.056

Sift

Benign

0.19

Sift4G

Benign

0.18

Polyphen

0.85

Vest4

0.29

MutPred

0.46

Gain of sheet (P = 0.0049)

MVP

0.48

MPC

0.18

ClinPred

0.33

GERP RS

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.081

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over